title: Screening for GNAS genetic and epigenetic alterations in progressive osseous heteroplasia: first Italian series.
abstract: Progressive osseous heteroplasia (POH) is a rare autosomal dominant disorder of mesenchymal differentiation characterized by progressive heterotopic ossification (HO) of dermis, deep connective tissues and skeletal muscle. Usually, initial bone formation occurs during infancy as primary osteoma cutis (OC) then progressively extending into deep connective tissues and skeletal muscle over childhood. Most cases of POH are caused by paternally inherited inactivating mutations of GNAS gene. Maternally inherited mutations as well as epigenetic defects of the same gene lead to pseudohypoparathyroidism (PHP) and Albright's hereditary osteodystrophy (AHO). During the last decade, some reports documented the existence of patients with POH showing additional features characteristic of AHO such as short stature and brachydactyly, previously thought to occur only in other GNAS-associated disorders. Thus, POH can now be considered as part of a wide spectrum of ectopic bone formation disorders caused by inactivating GNAS mutations. Here, we report genetic and epigenetic analyses of GNAS locus in 10 patients affected with POH or primary OC, further expanding the spectrum of mutations associated with this rare disease and indicating that, unlike PHP, methylation alterations at the same locus are absent or uncommon in this disorder.
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Endocrinology and Diabetology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via F. Sforza 35, 20122 Milano, Italy.
authors.forename: F M
authors.initials: FM
authors.lastname: Elli
authors.forename: A M
authors.initials: AM
authors.lastname: Barbieri
authors.forename: P
authors.initials: P
authors.lastname: Bordogna
authors.forename: P
authors.initials: P
authors.lastname: Ferrari
authors.forename: R
authors.initials: R
authors.lastname: Bufo
authors.forename: E
authors.initials: E
authors.lastname: Ferrante
authors.forename: E
authors.initials: E
authors.lastname: Giardino
authors.forename: P
authors.initials: P
authors.lastname: Beck-Peccoz
authors.forename: A
authors.initials: A
authors.lastname: Spada
authors.forename: G
authors.initials: G
authors.lastname: Mantovani
mesh_terms: D000293:Adolescent; D001851:Bone Diseases, Metabolic / Q000175:diagnosis* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002864:Chromogranins; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009999:Ossification, Heterotopic / Q000175:diagnosis* / Q000235:genetics*; D012873:Skin Diseases, Genetic / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs
keywords: GNAS; Heterotopic ossification (HO); Osteoma cutis (OC); Progressive osseous heteroplasia (POH)